Biliary tract cancer (BTC) is a neoplasm that accounts for 3% of all gastrointestinal cancers and 15% of all primary liver cancers. During the last two decades, the incidence of BTC is rising, mainly due to an increase in the intrahepatic form (Khan, S. A. et al., “Cholangiocarcinoma,” Lancet, 366:1303-14 (2005); Patel, T. et al., “Cholangiocarcinoma,” Nat Clin Pract Gastroentel Hepatol, 3:33-42 (2006)). North Thailand has the highest incidence (Shaib, Y. et al., “The epidemiology of holangiocarcinoma,” Semin Liver Dis, 24:115-125 (2004)). Only chance to cure is complete surgical resection. For complete resection, diagnosis in early stage is important, but difficult. Even with margin free resection, 5-year survival figures only reach 20% to 40% (Jarmagin, W. R., et al., “Surgical management of cholangiocarcinoma,” Semin Liver Dis, 24:18 (2004); Gores, G. J., “Cholangocarcinoma: current concepts and insight,” Hepatology, 37:961-969 (2003)). Unresectable disease usually shows 6-month to 1-year survival time (Jarmagin, W. R., et al., “Surgical management of cholangiocarcinoma,” Semin Liver Dis, 24:18 (2004)). Almost one-third of the patients of BTC is too late for resection. Therefore, there is a need to establish a diagnostic process at the early stage of BTC.
Currently, diagnosis of BTC depends on imagings of the biliary tree such as computed tomography or ultrasonography or endscopic retrogradal cholangiograpy (ERC) in patients having clinical symptoms. Brush cytology by ERC can make a tissue diagnosis, but sensitivity is poor because of rich desemoplasitc nature of BTC (Gores, G. J., “Cholangocarcinoma: current concepts and insight,” Hepatology, 37:961-969 (2003); Abu-Hamda, E. M., et al., “Endoscopic management of cholagiocarcinoma,” Semin Liver Dis, 4:165-175 (2004)). Consequently clinicians often elucidate other diagnostic clues of malignancy, and tumor markers provide more information.
Serum tumor markers, carcinoembryonic antigen (CEA) and carbon hydorate antigen 19.9 (CA19-9) are used worldwide for diagnosis of BTC but they have poor sensitivity and specificity. Many reports represent the specificity of these markers are respectively 50% and 70% (Nehls, O. et al., “Serum and Bile markers for cholangiocarcinoma,” Semin Liver Dis, 24:139-154 (2004)). Therefore, there is a need for new markers of BTC. Before now, a proteomic technique has been used with a number of other malignancy to discover potential markers such as ovarian (Rai, A. J. et al., “Proteomic approaches to tumor marker discovery,” Arch Pathol Lab Med, 126:1518-1526 (2002); Kozak, K. R., et al., “Identification of biomarkers for ovarian cancer using strong anion-ex-change Protein chip,” 100:12343-12348 (2003); Petricoin, E. F., et al., “Use of proteomic patterns in serum to identify ovarian cancer,” Lancet, 359:572-577, (2002)), pancreatic (Rosty, C. et al., “Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology,” Cancer Res, 62:1868-1875 (2002); Koopmann, J, et al., “Serum diagnosis of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass spectrometry,” Clin Cancer Res, 10:860-868 (2004); Yu, Y., et al., “Prediction of pancreatic cancer by serum biomarkers using surface-enhanced laser desorption/ionization-based decision tree classification,” Oncology, 68:79-86 (2005), head and neck (Yu, Y. et al., “Prediction of pancreatic cancer by serum biomarkers using surface-enhanced laser desorption/ionization-based decision tree classification,” Oncology, 68:79-86 (2005); Wadsworth, J. T. et al., “Identification of patients with head and neck cancer using serum protein profiles,” Arch Otolarygol Head Neck Surg, 130:98-104 (2004)), using SurfaceEnhancedlaser Desorption and Ionization Mass Spectrometry (SELDI-TOF-MS).
Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) represents a key tool for rapidly analyzing clinical blood samples. The advantages of this method are its high-throughput capability and small sample size necessary for the analysis. Therefore, the inventors sought to identify a new biomarker of BTC with this technique and analyzed the serum profiling of the low molecular weight peptides with MALDI-TOF mass spectrometry in patients with BTC.